Acetylcholine is the chemical mediator at all synapses between preganglionic and postganglionic fibers of the autonomic nervous systems, which has an important effect on control of smooth muscle and controls many internal functions. Acetylcholine is also a chemical mediator at all myoneural junctions, all postganglionic parasympathetic and some postganglionic sympathetic endings. Acetylcholine molecules are released into the synaptic cleft by a mechanism which is not fully understood and, once released, diffuse across the cleft and combine with receptor molecules (acetylcholine receptors or AChRs) present in the postsynaptic neuron membrane or muscle cell membrane. At the neuromuscular junction, as at other chemical synapses, the number and distribution of neurotransmitter receptors is a critical factor in determining the response to presynaptic stimulation.
A key event in the formulation of the neuromuscular junction is the accumulation of acetylcholine receptors in the muscle membrane opposed to the nerve terminal. It is known that at the mature neuromuscular junction, AChRs are packed in the postsynaptic membrane and highly localized. That is, receptors are present in the postsynaptic membrane at a density in excess of 10,000/.mu.m.sup.2 and more than 70% of the receptors are restricted to the endplate, which comprises less than 0.1% of the muscle surface membrane. Little is known about how AChRs are inserted into and localized within the neuromuscular junction.